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  1. Article ; Online: Multifunctional Cationic Hyperbranched Polyaminoglycosides that Target Multiple Mediators for Severe Abdominal Trauma Management

    Yongqiang Xiao / He Fang / Yuefei Zhu / Jie Zhou / Zhanzhan Dai / Hongxia Wang / Zhaofan Xia / Zhaoxu Tu / Kam W. Leong

    Advanced Science, Vol 11, Iss 1, Pp n/a-n/a (2024)

    2024  

    Abstract: Abstract Trauma and its associated complications, including dysregulated inflammatory responses, severe infection, and disseminated intravascular coagulation (DIC), continue to pose lethal threats worldwide. Following injury, cell‐free nucleic acids ( ... ...

    Abstract Abstract Trauma and its associated complications, including dysregulated inflammatory responses, severe infection, and disseminated intravascular coagulation (DIC), continue to pose lethal threats worldwide. Following injury, cell‐free nucleic acids (cfNAs), categorized as damage‐associated molecular patterns (DAMPs), are released from dying or dead cells, triggering local and systemic inflammatory responses and coagulation abnormalities that worsen disease progression. Harnessing cfNA scavenging strategies with biomaterials has emerged as a promising approach for treating posttrauma systemic inflammation. In this study, the effectiveness of cationic hyperbranched polyaminoglycosides derived from tobramycin (HPT) and disulfide‐included HPT (ss‐HPT) in scavenging cfNAs to mitigate posttrauma inflammation and hypercoagulation is investigated. Both cationic polymers demonstrate the ability to suppress DAMP‐induced toll‐like receptor (TLR) activation, inflammatory cytokine secretion, and hypercoagulation by efficiently scavenging cfNAs. Additionally, HPT and ss‐HPT exhibit potent antibacterial efficacy attributed to the presence of tobramycin in their chemical composition. Furthermore, HPT and ss‐HPT exhibit favorable modulatory effects on inflammation and therapeutic outcomes in a cecal ligation puncture (CLP) mouse abdominal trauma model. Notably, in vivo studies reveal that ss‐HPT displayed high accumulation and retention in injured organs of traumatized mice while maintaining a higher biodegradation rate in healthy mice, contrasting with findings for HPT. Thus, functionalized ss‐HPT, a bioreducible polyaminoglycoside, holds promise as an effective option to enhance therapeutic outcomes for trauma patients by alleviating posttrauma inflammation and coagulation complications.
    Keywords abdominal trauma ; antibacterial properties ; anticoagulation ; biodegradable polyaminoglycoside ; cfNA scavenging ; inflammation modulation ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2024-01-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: A Versatile and Robust Platform for the Scalable Manufacture of Biomimetic Nanovaccines

    Hanze Hu / Chao Yang / Fan Zhang / Mingqiang Li / Zhaoxu Tu / Lizhong Mu / Jianati Dawulieti / Yeh‐Hsing Lao / Zixuan Xiao / Huize Yan / Wen Sun / Dan Shao / Kam W. Leong

    Advanced Science, Vol 8, Iss 15, Pp n/a-n/a (2021)

    2021  

    Abstract: Abstract Biomimetic strategies are useful for designing potent vaccines. Decorating a nanoparticulate adjuvant with cell membrane fragments as the antigen‐presenting source exemplifies, such as a promising strategy. For translation, a standardizable, ... ...

    Abstract Abstract Biomimetic strategies are useful for designing potent vaccines. Decorating a nanoparticulate adjuvant with cell membrane fragments as the antigen‐presenting source exemplifies, such as a promising strategy. For translation, a standardizable, consistent, and scalable approach for coating nanoadjuvant with the cell membrane is important. Here a turbulent mixing and self‐assembly method called flash nanocomplexation (FNC) for producing cell membrane‐coated nanovaccines in a scalable manner is demonstrated. The broad applicability of this FNC technique compared with bulk‐sonication by using ten different core materials and multiple cell membrane types is shown. FNC‐produced biomimetic nanoparticles have promising colloidal stability and narrow particle polydispersity, indicating an equal or more homogeneous coating compared to the bulk‐sonication method. The potency of a nanovaccine comprised of B16‐F10 cancer cell membrane decorating mesoporous silica nanoparticles loaded with the adjuvant CpG is then demonstrated. The FNC‐fabricated nanovaccines when combined with anti‐CTLA‐4 show potency in lymph node targeting, DC antigen presentation, and T cell immune activation, leading to prophylactic and therapeutic efficacy in a melanoma mouse model. This study advances the design of a biomimetic nanovaccine enabled by a robust and versatile nanomanufacturing technique.
    Keywords biomimetics ; cancer vaccine ; cell membrane ; flash nanocomplexation ; mesoporous silica nanoparticles ; Science ; Q
    Subject code 620
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Dose‐Dependent Carbon‐Dot‐Induced ROS Promote Uveal Melanoma Cell Tumorigenicity via Activation of mTOR Signaling and Glutamine Metabolism

    Yi Ding / Jie Yu / Xingyu Chen / Shaoyun Wang / Zhaoxu Tu / Guangxia Shen / Huixue Wang / Renbing Jia / Shengfang Ge / Jing Ruan / Kam W. Leong / Xianqun Fan

    Advanced Science, Vol 8, Iss 8, Pp n/a-n/a (2021)

    2021  

    Abstract: Abstract Uveal melanoma (UM) is the most common intraocular malignant tumor in adults and has a low survival rate following metastasis; it is derived from melanocytes susceptible to reactive oxygen species (ROS). Carbon dot (Cdot) nanoparticles are a ... ...

    Abstract Abstract Uveal melanoma (UM) is the most common intraocular malignant tumor in adults and has a low survival rate following metastasis; it is derived from melanocytes susceptible to reactive oxygen species (ROS). Carbon dot (Cdot) nanoparticles are a promising tool in cancer detection and therapy due to their unique photophysical properties, low cytotoxicity, and efficient ROS productivity. However, the effects of Cdots on tumor metabolism and growth are not well characterized. Here, the effects of Cdots on UM cell metabolomics, growth, invasiveness, and tumorigenicity are investigated in vitro and in vivo zebrafish and nude mouse xenograft model. Cdots dose‐dependently increase ROS levels in UM cells. At Cdots concentrations below 100 µg mL−1, Cdot‐induced ROS promote UM cell growth, invasiveness, and tumorigenicity; at 200 µg mL−1, UM cells undergo apoptosis. The addition of antioxidants reverses the protumorigenic effects of Cdots. Cdots at 25–100 µg mL−1 activate Akt/mammalian target of rapamycin (mTOR) signaling and enhance glutamine metabolism, generating a cascade that promotes UM cell growth. These results demonstrate that moderate, subapoptotic doses of Cdots can promote UM cell tumorigenicity. This study lays the foundation for the rational application of ROS‐producing nanoparticles in tumor imaging and therapy.
    Keywords glutamine ; metabolomics ; mTOR ; ROS ; uveal melanoma ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article: pH-degradable PVA-based nanogels via photo-crosslinking of thermo-preinduced nanoaggregates for controlled drug delivery

    Chen, Wei / Lingyan Gao / Rainer Haag / Yong Hou / Zhaoxu Tu

    Journal of Controlled Release. 2016,

    2016  

    Abstract: pH-Degradable PVA nanogels, which are prepared by photo-crosslinking thermo-preinduced PVA nanoaggregates in water without any surfactants or toxic organic solvents, are used for intracellular PTX release and anticancer treatment. These nanogels fast ... ...

    Abstract pH-Degradable PVA nanogels, which are prepared by photo-crosslinking thermo-preinduced PVA nanoaggregates in water without any surfactants or toxic organic solvents, are used for intracellular PTX release and anticancer treatment. These nanogels fast degraded at mildly acidic conditions with a pH-triggered PTX release, and the degradation products are only native PVA and poly(hydroxyethyl acrylate) (PHEA) as well as acetaldehyde without any toxic byproducts. The nanogel sizes could be tailored by different temperatures during the crosslinking process. The results of confocal microscopy and flow cytometry revealed that smaller nanogels exhibited enhanced internalization with MCF-7 cells than the ones treated with larger nanogels, by which the smaller PTX-loaded nanogels induced a more significant cytotoxicity against MCF-7 cells.pH-Degradable PVA nanogels can be prepared by photo-crosslinking of thermo-preinduced nanoaggregates with tailored nanogel sizes given their pH-triggered PTX release and fast acid-degradation into native PVA and cell-compatible poly(hydroxyethyl acrylate) (PHEA) as well as acetaldehyde.
    Keywords acetaldehyde ; byproducts ; confocal microscopy ; crosslinking ; cytotoxicity ; drugs ; flow cytometry ; nanoparticles ; solvents ; surfactants ; temperature
    Language English
    Size p. .
    Publishing place Elsevier B.V.
    Document type Article
    Note Pre-press version
    ZDB-ID 632533-6
    ISSN 1873-4995 ; 0168-3659
    ISSN (online) 1873-4995
    ISSN 0168-3659
    DOI 10.1016/j.jconrel.2016.10.032
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Janus Nanobullets Combine Photodynamic Therapy and Magnetic Hyperthermia to Potentiate Synergetic Anti‐Metastatic Immunotherapy

    Zheng Wang / Fan Zhang / Dan Shao / Zhimin Chang / Lei Wang / Hanze Hu / Xiao Zheng / Xuezhao Li / Fangman Chen / Zhaoxu Tu / Mingqiang Li / Wen Sun / Li Chen / Wen‐Fei Dong

    Advanced Science, Vol 6, Iss 22, Pp n/a-n/a (2019)

    2019  

    Abstract: Abstract Photodynamic therapy (PDT) is clinically promising in destructing primary tumors but ineffective against distant metastases. This study reports the use of immunogenic nanoparticles mediated combination of PDT and magnetic hyperthermia to ... ...

    Abstract Abstract Photodynamic therapy (PDT) is clinically promising in destructing primary tumors but ineffective against distant metastases. This study reports the use of immunogenic nanoparticles mediated combination of PDT and magnetic hyperthermia to synergistically augment the anti‐metastatic efficacy of immunotherapy. Janus nanobullets integrating chlorine e6 (Ce6) loaded, disulfide‐bridged mesoporous organosilica bodies with magnetic heads (M‐MONs@Ce6) are tailored for redox/pH‐triggered photosensitizer release accompanying their matrix degradation. Cancer cell membrane cloaking enables favorable tumor‐targeted accumulation and prolonged blood circulation time of M‐MONs@Ce6. The combination of PDT and magnetic hyperthermia has a strong synergy anticancer activity and simultaneously elicits a sequence of immunogenic cell death, resulting in synergistically tumor‐specific immune responses. When combined with anti‐CTLA‐4 antibody, the biomimetic and biodegradable nanoparticle enables the notable eradication of primary and deeply metastatic tumors with low systematic toxicity, thus potentially advancing the development of combined hyperthermia, PDT, and checkpoint blockade immunotherapy to combat cancer metastasis.
    Keywords cancer metastasis ; checkpoint blockade immunotherapy ; Janus nanoparticles ; magnetic hyperthermia ; photodynamic therapy ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2019-11-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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